Multi-omics Prognostic Analysis of Lysine Acetylation Regulators in Glioma

Abstract

Background: Lysine acetylation is a crucial kind of protein modification and is related to the malignant development of various cancers. But their roles in glioma are still unclear and needed concluded comprehensively. Methods: In this study, we comprehensively analyzed the expression levels of 33 lysine acetylation regulators (LARs) and prognostic roles by using public data, including the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). The prognostic roles of LARs were judged by univariate Cox regression. Consensus clustering was applied to result in three stratified glioma subtypes (LA1, 2, and 3) with different clinical outcomes. We also constructed a risk signature for predicting the overall survival of glioma patients by using least absolute shrinkage and selection operator regression (LASSO regression). Besides, copy number variations (CNVs) and single nucleotide polymorphism (SNP) of LARs were also analyzed in our study. Results: We found the mRNA expression levels of most of LARs were dysregulated in gliomas and associated with the prognosis of glioma patients. The risk signature constructed by 14 LARs presented an independent prognostic role in both the CGGA (HR:1.96, 95%CI:1.33-2.90) and TCGA (HR:1.48, 95%CI:1.08-2.03) datasets and robust predictive effects in the ROC curves with all of area under curves more than 0.800. Moreover, the copy number variations of LARs were also significantly related to the prognosis of glioma patients, in which HDAC1 (1p) was one of the oncogenes lost in 1p/19q codeletion events, while SIRT2 (19q) and EP300 (22q) may act as tumor suppressors in gliomas with 19q or 22q deletions, respectively. Conclusion: LARs are potential biomarkers for the malignant progression of gliomas, and our results could be useful for predicting the OS of glioma patients and provide some clues in searching the functions of LARs in glioma progression. Keywords: glioma, lysine acetylation regulator, epigenetic, prognostic signature, biomarker.